Publications

• Ubiquinone biosynthesis in Saccharomyces cerevisiae. Isolation and sequence of COQ3, the 3,4-dihydroxy-5-hexaprenylbenzoate methyltransferase gene.

  Clarke C.F., Williams W., Teruya J.H.

  Ubiquinone (or coenzyme Q) is a lipid component of the respiratory chain in the inner mitochondrial membrane, in which it functions in electron transport. Recent reports show that ubiquinone and ubiquinone biosynthetic enzymes are present in both mitochondrial and nonmitochondrial membranes of cel ... >> More

  Ubiquinone (or coenzyme Q) is a lipid component of the respiratory chain in the inner mitochondrial membrane, in which it functions in electron transport. Recent reports show that ubiquinone and ubiquinone biosynthetic enzymes are present in both mitochondrial and nonmitochondrial membranes of cells (Kalen, A., Appelkvist, E.-L., Chojnacki, T., and Dallner, G. (1990) J. Biol. Chem. 265, 1158-1164) although the functions that ubiquinone may play outside of the mitochondrion are not understood. To study coenzyme Q synthesis and function we cloned the 3,4-dihydroxy-5-hexaprenylbenzoate (DHHB) methyltransferase gene by functional complementation of a yeast coenzyme Q mutant strain, defective in the COQ3 gene (Tzagoloff, A., and Dieckmann, C. L. (1990) Microbiol. Rev. 54, 211-225). This gene restores both coenzyme Q synthesis in the mutant strain and the ability to grow on media containing glycerol, a nonfermentable substrate. A one-step in situ gene replacement with the cloned DHHB methyltransferase DNA directs integration to the yeast COQ3 locus on chromosome XV of Saccharomyces cerevisiae, establishing that the COQ3 locus encodes the DHHB methyltransferase structural gene. The predicted amino acid sequence of the yeast DHHB methyltransferase contains a methyltransferase consensus sequence and shows a 40% identity with an open reading frame of Escherichia coli, the gyrA5' hypothetical protein. This open reading frame is adjacent to the gyrA gene and close to the mapped location of the ubiG gene at 48 min on the E. coli chromosome. These results suggest that the E. coli gyrA5' open reading frame encodes a methyltransferase and may correspond to the ubiG gene, which is required for ubiquinone biosynthesis. << Less

  J. Biol. Chem. 266:16636-16644(1991) [PubMed] [EuropePMC]

• Regulation of coenzyme Q biosynthesis in yeast: a new complex in the block.

  Gonzalez-Mariscal I., Garcia-Teston E., Padilla S., Martin-Montalvo A., Pomares-Viciana T., Vazquez-Fonseca L., Gandolfo-Dominguez P., Santos-Ocana C.

  Coenzyme Q (CoQ) is an isoprenylated benzoquinone found in mitochondria, which functions mainly as an electron carrier from complex I or II to complex III in the inner membrane. CoQ is also an antioxidant that specifically prevents the oxidation of lipoproteins and the plasma membrane. Most of the ... >> More

  Coenzyme Q (CoQ) is an isoprenylated benzoquinone found in mitochondria, which functions mainly as an electron carrier from complex I or II to complex III in the inner membrane. CoQ is also an antioxidant that specifically prevents the oxidation of lipoproteins and the plasma membrane. Most of the information about the synthesis of CoQ comes from studies performed in Saccharomyces cerevisiae. CoQ biosynthesis is a highly regulated process of sequential modifications of the benzene ring. There are three pieces of evidence supporting the involvement of a multienzymatic complex in yeast CoQ6 biosynthesis: (a) the accumulation of a unique early precursor in all null mutants of the COQ genes series, 4-hydroxy-3-hexaprenyl benzoate (HHB), (b) the lack of expression of several Coq proteins in COQ null mutants, and (c) the restoration of CoQ biosynthesis complex after COQ8 overexpression. The model we propose based on the formation of a multiprotein complex should facilitate a better understanding of CoQ biosynthesis. According to this model, the complex assembly requires the synthesis of a precursor such as HHB by Coq2p that must be recognized by the regulatory protein Coq4p to act as the core component of the complex. The phosphorylation of Coq3p and Coq5p by the kinase Coq8p facilitates the formation of an initial precomplex of 700 kDa that contains all Coq proteins with the exception of Coq7p. The precomplex is required for the synthesis of 5-demethoxy-Q6 , the substrate of Coq7p. When cells require de novo CoQ6 synthesis, Coq7p is dephosphorylated by Ptc7p, a mitochondrial phosphatase that activates the synthesis of CoQ6. This event allows for the full assembly of a complex of 1,300 kDa that is responsible for the final product of the pathway, CoQ6 . << Less

  IUBMB Life 66:63-70(2014) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Yeast and rat Coq3 and Escherichia coli UbiG polypeptides catalyze both O-methyltransferase steps in coenzyme Q biosynthesis.

  Poon W.W., Barkovich R.J., Hsu A.Y., Frankel A., Lee P.T., Shepherd J.N., Myles D.C., Clarke C.F.

  Ubiquinone (coenzyme Q or Q) is a lipid that functions in the electron transport chain in the inner mitochondrial membrane of eukaryotes and the plasma membrane of prokaryotes. Q-deficient mutants of Saccharomyces cerevisiae harbor defects in one of eight COQ genes (coq1-coq8) and are unable to gr ... >> More

  Ubiquinone (coenzyme Q or Q) is a lipid that functions in the electron transport chain in the inner mitochondrial membrane of eukaryotes and the plasma membrane of prokaryotes. Q-deficient mutants of Saccharomyces cerevisiae harbor defects in one of eight COQ genes (coq1-coq8) and are unable to grow on nonfermentable carbon sources. The biosynthesis of Q involves two separate O-methylation steps. In yeast, the first O-methylation utilizes 3, 4-dihydroxy-5-hexaprenylbenzoic acid as a substrate and is thought to be catalyzed by Coq3p, a 32.7-kDa protein that is 40% identical to the Escherichia coli O-methyltransferase, UbiG. In this study, farnesylated analogs corresponding to the second O-methylation step, demethyl-Q(3) and Q(3), have been chemically synthesized and used to study Q biosynthesis in yeast mitochondria in vitro. Both yeast and rat Coq3p recognize the demethyl-Q(3) precursor as a substrate. In addition, E. coli UbiGp was purified and found to catalyze both O-methylation steps. Futhermore, antibodies to yeast Coq3p were used to determine that the Coq3 polypeptide is peripherally associated with the matrix-side of the inner membrane of yeast mitochondria. The results indicate that one O-methyltransferase catalyzes both steps in Q biosynthesis in eukaryotes and prokaryotes and that Q biosynthesis is carried out within the matrix compartment of yeast mitochondria. << Less

  J. Biol. Chem. 274:21665-21672(1999) [PubMed] [EuropePMC]

  This publication is cited by 7 other entries.